Pravastatin is a member of the class of pharmaceutical compounds called statins. Statins currently are the most effective treatment for lowering serum cholesterol levels in patients with atherosclerosis and hypercholesteremia. Pravastatin is the common medicinal name of the chemical compound [1S-[1α(β*,δ*)2α,6α,8β(R*),8aα]]-1,2,6,7,8,8a-hexahydro-β,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-heptanoic acid. (CAS Registry No. 81093-37-0) The molecular structure of pravastatin is represented by Formula (I). “Pravastatin sodium” is defined as the monosodium salt of pravastatin, whether hydrated or anhydrous, solvated or unsolvated.

According to U.S. Pat. No. 4,346,227, incorporated herein by reference, pravastatin is reported as having been first isolated as a metabolite of compactin by M. Tanaka et al. during a study of compactin metabolism. The '227 patent discloses the isolation of pravastatin in its lactone form, as the methyl ester of the free carboxylic acid and as the monosodium salt of the free carboxylic acid (“pravastatin sodium”). Pravastatin sodium was analyzed by nuclear magnetic resonance spectroscopy, infrared (“IR”) spectroscopy, ultraviolet spectroscopy and thin layer chromatography. Pravastatin sodium was analyzed in solid form by IR spectroscopy using the conventional technique of co-mixing with potassium bromide (“KBr”) and then compressing to form a KBr window or pellet. The IR spectrum of the pravastatin sodium obtained by absorption bands at 3400, 2900, 1725, 1580 cm−1. All other spectral measurements are repeated on pravastatin sodium in solution.
The present invention relates to new crystal forms of pravastatin sodium and compositions containing them. Polymorphism is the property of some molecules and molecular complexes to assume more than one crystalline form in the solid state. A single molecule may give rise to a variety of crystal forms (also called “polymorphs”) having distinct physical properties. The existence of more than one crystal form can be determined in a laboratory by comparison of the angles at which X-ray radiation reflected from the forms undergoes constructive interference and by comparing the absorptions of incident infrared radiation at different wavelengths. The former technique is known as X-ray diffraction spectroscopy and the angles at which constructive interference occurs are known as reflections.
The differences in the physical properties of polymorphs result from the orientation and intermolecular interactions of adjacent molecules (complexes) in the bulk solid. Accordingly, polymorphs are distinct solids sharing the same molecular formula yet having distinct advantageous and/or disadvantageous physical properties compared to other forms in the polymorph family.
One of the most important physical properties of a polymorphic pharmaceutical compound is the solubility of each of its forms in aqueous solution, particularly the solubility in gastric juices of a patient. Other important properties relate to the ease of processing the form into pharmaceutical dosages, such as the tendency of a powdered or granulated form to flow and the surface properties that determine whether crystals of the form will adhere to each other when compacted into a tablet.